Journal: Drug metabolism and disposition: the biological fate of chemicals

Article Title: Evaluation of Clopidogrel Conjugation Metabolism: PK Studies in Man and Mice of Clopidogrel Acyl Glucuronide.

doi: 10.1124/dmd.116.071092

Figure Lengend Snippet: Fig. 2. Metabolites determined in plasma after administration of clopidogrel acyl glucuronide by intravenous (N = 35, parallel, 5 animals per sampling point) and oral route (N = 30 parallel, 5 animals per sampling point).

Article Snippet: The internal standards used for high-performance liquid chromatography– tandem mass spectrometry (HPLC–MS/MS) analytical determinations were: d3-clopidogrel hydrogen sulfate (SynFine Research, RichmondHill, ON, Canada), clopidogrel acyl-b- D-glucuronide (Toronto Research Chemicals Inc.), and 13C6-clopidogrel carboxylic acid (Alsachim, Illkirch-Graffenstaden, France).

Techniques: Clinical Proteomics, Sampling

Journal: Drug metabolism and disposition: the biological fate of chemicals

Article Title: Evaluation of Clopidogrel Conjugation Metabolism: PK Studies in Man and Mice of Clopidogrel Acyl Glucuronide.

doi: 10.1124/dmd.116.071092

Figure Lengend Snippet: Fig. 3. Plasma concentration-versus-time curves for the three analytes after administration of clopidogrel in human subjects (N = 6) with and without charcoal (linear-linear display on A, C, E and ln-linear display on B, D, F).

Article Snippet: The internal standards used for high-performance liquid chromatography– tandem mass spectrometry (HPLC–MS/MS) analytical determinations were: d3-clopidogrel hydrogen sulfate (SynFine Research, RichmondHill, ON, Canada), clopidogrel acyl-b- D-glucuronide (Toronto Research Chemicals Inc.), and 13C6-clopidogrel carboxylic acid (Alsachim, Illkirch-Graffenstaden, France).

Techniques: Clinical Proteomics, Concentration Assay

Journal: Drug metabolism and disposition: the biological fate of chemicals

Article Title: Evaluation of Clopidogrel Conjugation Metabolism: PK Studies in Man and Mice of Clopidogrel Acyl Glucuronide.

doi: 10.1124/dmd.116.071092

Figure Lengend Snippet: Fig. 4. Total recovery of clopidogrel, clopidogrel acyl-glucuronide, and clopidogrel carboxylic acid in urine and stool samples over 72 hours postdose after administration of clopidogrel in human subjects (N = 6).

Article Snippet: The internal standards used for high-performance liquid chromatography– tandem mass spectrometry (HPLC–MS/MS) analytical determinations were: d3-clopidogrel hydrogen sulfate (SynFine Research, RichmondHill, ON, Canada), clopidogrel acyl-b- D-glucuronide (Toronto Research Chemicals Inc.), and 13C6-clopidogrel carboxylic acid (Alsachim, Illkirch-Graffenstaden, France).

Techniques:

Journal: Drug metabolism and disposition: the biological fate of chemicals

Article Title: Evaluation of Clopidogrel Conjugation Metabolism: PK Studies in Man and Mice of Clopidogrel Acyl Glucuronide.

doi: 10.1124/dmd.116.071092

Figure Lengend Snippet: Fig. 5. Total recovery of clopidogrel, clopidogrel acyl-glucuronide, and clopidogrel carboxylic acid in urine samples after administration of clopidogrel in human subjects (N = 6) with or without activated charcoal.

Article Snippet: The internal standards used for high-performance liquid chromatography– tandem mass spectrometry (HPLC–MS/MS) analytical determinations were: d3-clopidogrel hydrogen sulfate (SynFine Research, RichmondHill, ON, Canada), clopidogrel acyl-b- D-glucuronide (Toronto Research Chemicals Inc.), and 13C6-clopidogrel carboxylic acid (Alsachim, Illkirch-Graffenstaden, France).

Techniques:

Journal: Drug metabolism and disposition: the biological fate of chemicals

Article Title: Evaluation of Clopidogrel Conjugation Metabolism: PK Studies in Man and Mice of Clopidogrel Acyl Glucuronide.

doi: 10.1124/dmd.116.071092

Figure Lengend Snippet: Fig. 6. Recovery of clopidogrel acyl-glucuronide in urine (N = 6) displayed by collection intervals (A) and amount of urine excreted by collection intervals (B).

Article Snippet: The internal standards used for high-performance liquid chromatography– tandem mass spectrometry (HPLC–MS/MS) analytical determinations were: d3-clopidogrel hydrogen sulfate (SynFine Research, RichmondHill, ON, Canada), clopidogrel acyl-b- D-glucuronide (Toronto Research Chemicals Inc.), and 13C6-clopidogrel carboxylic acid (Alsachim, Illkirch-Graffenstaden, France).

Techniques:

Journal: African Journal of Pharmacy and Pharmacology

Article Title: Pharmacokinetics of 600 mg loading dose of clopidogrel in patients undergoing percutaneous coronary intervention

doi: 10.5897/ajpp12.352

Figure Lengend Snippet: Figure 1. HPLC chromatogram of carboxylic acid metabolite of clopidogrel and internal standard (IS). Plasma sample spiked with clopidogrel carboxylate metabolite and IS; Peaks: 1, IS; 2, clopidogrel carboxylate acid metabolite. RESULTS Chromatographic condition Under the chromatographic conditions described, the drug and IS were well resolved in plasma samples and eluted at 4.44 and 2.85 min, respectively. No interfering peaks of endogenous plasma components were found at the retention time of metabolite or internal standard in blank plasma (Figure 1) Method development and validation Linearity A linear relationship was obtained between the peak area

Article Snippet: Clopidogrel carboxylic acid was obtained from Toronto Research Chemicals in Canada.

Techniques: Clinical Proteomics, Biomarker Discovery

Journal: bioRxiv

Article Title: Microglial P2Y12 mediates chronic stress-induced synapse loss in the prefrontal cortex and associated behavioral consequences in male mice

doi: 10.1101/2022.03.16.484487

Figure Lengend Snippet: A . Male wild-type or Thy1-GFP(M) mice were exposed to 14 days of chronic unpredictable stress (CUS) or were handled as controls. During this time, animals received daily injections of either vehicle, clopidogrel, or ticagrelor. One cohort was subjected to behavioral testing ( n = 9-20/group). B . Average time spent immobile in the forced swim test (FST). C . Average time spent exploring objects in the temporal object recognition task (TOR). D . Discrimination index in the TOR. E . In a separate cohort of mice, brains were extracted, frontal cortex was dissected out, and microglia were isolated and characterized using flow cytometry ( n = 7-22/group). Normalized mean fluorescence intensity of P2Y12, CSF1R, CD11b, and CX3CR1 in frontal cortex microglia. Normalized mean side scatter profile is shown. Bars represent mean ± S.E.M. * p <0.05 compared to same-treatment unstressed animal. # p <0.05 compared to unstressed vehicle-treated animal.

Article Snippet: Clopidogrel sulfate (LKT Laboratories, St Paul, MN; C4658) was diluted to 5 mg/ml in 0.9% sodium chloride.

Techniques: Isolation, Flow Cytometry, Fluorescence

Journal: bioRxiv

Article Title: Microglial P2Y12 mediates chronic stress-induced synapse loss in the prefrontal cortex and associated behavioral consequences in male mice

doi: 10.1101/2022.03.16.484487

Figure Lengend Snippet: Male Thy1-GFP(M) mice were exposed to 14 days of chronic unpredictable stress (CUS) or were handled as controls. During this time, animals received daily injections of either vehicle or clopidogrel. Approximately 4 hours after the final stressor, mice were perfused and brains were collected, sectioned, immunostained, and imaged ( n = 6-8/group). A . Confocal images of microglial IBA1 (red) and P2Y12 (cyan) in the mPFC. White scale bar represents 100 μm. B . Average number of FosB+ cells/mm 2 in the mPFC. C . Average number of IBA1+ cells/mm 2 in the mPFC. D . Average IBA1+ area per microglial cell. E . Average intensity (A.U.) of P2Y12 staining per microglial cell (relative to vehicle treated control group). F . Confocal images of microglia (IBA1, red) and dendritic segments (Thy1-GFP, green) were obtained from lamina I of the mPFC. Alongside merged channels, an orthogonal cross-section (matching the noted location) and representative dendritic segment is depicted for groups exposed to CUS. Microglial processes in close proximity to dendritic elements are noted within dashed circles, arrows indicate a dendritic element localized within a microglial cell body or process extension. White scale bar represents 5 μm. See Fig.S9 for additional images. G . Average dendritic spine density. H . Proportion of microglia with GFP+ inclusions. I . Number of GFP+ inclusions within microglia with dendritic elements. J . Average GFP+ inclusion volume per phagocytic microglia. * p <0.05 compared to same-treatment unstressed animal. # p <0.05 compared to unstressed vehicle-treated animal.

Article Snippet: Clopidogrel sulfate (LKT Laboratories, St Paul, MN; C4658) was diluted to 5 mg/ml in 0.9% sodium chloride.

Techniques: Staining, Control

Journal: The Korean Journal of Pain

Article Title: Pharmacological interactions between intrathecal pregabalin plus tianeptine or clopidogrel in a rat model of neuropathic pain

doi: 10.3344/kjp.2022.35.1.59

Figure Lengend Snippet: Time course curves of intrathecal pregabalin (A), tianeptine (B) and clopidogrel (C) on the hind paw withdrawal response after spinal nerve ligation. Data are presented as the withdrawal threshold (g). Each line represents the means ± standard error of the mean of 6 rats.

Article Snippet: Co., Ltd., Seoul, Korea), and clopidogrel hydrogen sulfate (Tocris Bioscience, Bristol, UK); all drugs were dissolved in saline.

Techniques: Ligation

Journal: The Korean Journal of Pain

Article Title: Pharmacological interactions between intrathecal pregabalin plus tianeptine or clopidogrel in a rat model of neuropathic pain

doi: 10.3344/kjp.2022.35.1.59

Figure Lengend Snippet: Dose response effect of intrathecal pregabalin, tianeptine and clopidogrel (A), or mixture of pregabalin and tianeptine (B) on the hind paw withdrawal response after spinal nerve ligation. Data are presented as the percent of maximal possible effect (% MPE). Each line represents the means ± standard error of the mean of 6 rats. P: pregabalin ED 50 , T: tianeptine ED 50 , ED 50 : 50% effective dose. * P < 0.05, *** P < 0.001, compared with vehicle.

Article Snippet: Co., Ltd., Seoul, Korea), and clopidogrel hydrogen sulfate (Tocris Bioscience, Bristol, UK); all drugs were dissolved in saline.

Techniques: Ligation

Journal: The Korean Journal of Pain

Article Title: Pharmacological interactions between intrathecal pregabalin plus tianeptine or clopidogrel in a rat model of neuropathic pain

doi: 10.3344/kjp.2022.35.1.59

Figure Lengend Snippet: A fixed dose analysis for the interaction between intrathecal clopidogrel (300 μg) and pregabalin. Data are presented as the percent of maximal possible effect (% MPE). Each line represents the means ± standard error of the mean of 6 rats.

Article Snippet: Co., Ltd., Seoul, Korea), and clopidogrel hydrogen sulfate (Tocris Bioscience, Bristol, UK); all drugs were dissolved in saline.

Techniques: